Pulmonary carcinogenesis: what role is played by the local microbiota?

The presence of commensal bacteria in the lower airways could lead to positive regulation of cell signaling pathways and be at the root of some lung cancers.

The involvement of the microbiota of the lower airways in the development of some lung cancers has been documented, but pathogenic mechanisms at work are still unclear. This unknown element spurred an American team to link pulmonary dysbiosis to up-regulation of the PI3K* signaling pathway, known to promote cell proliferation and tumoral invasion. Oral and bronchial cell samples were taken from 85 subjects (39 presenting with pulmonary tumors, 36 with benign nodules and 10 “healthy” controls). The objective was to characterize the bacterial populations and their metabolites likely to upregulate some signaling pathways that promote carcinogenesis.

Carcinogenic dysbiosis confirmed in vitro

The composition of the pulmonary microbiota of cancer patients proved to be significantly different from that of the other groups. Two bacterial genera usually found in the oral cavity were particularly represented: Streptococcus and Veillonella. This overabundance was accompanied by up-regulation of the PI3K and ERK signaling pathways, with similar functions. In order to confirm the causal link, the team then exposed lung epithelial cells in vitro to different bacterial genera, including Streptococcus, Veillonella and Prevotella, a commensal bacterium of the oral microbiota known to be predictive of lung cancer. An up-regulation of the PI3K and ERK signaling pathways was observed, which confirmed the original hypothesis.

The pulmonary microbiota: a promising target?

The researchers consider that additional studies will be necessary to identify the metabolites and the intermediate pathways involved in activation of PI3K and ERK signaling pathways. These results nevertheless improve the understanding of the effects of pulmonary dysbiosis on lung cancer pathogenesis and allow new therapeutic anti-cancer approaches targeting the local microbiota to be envisaged.

*PI3K = phosphoinositide 3-kinase: intracellular signaling pathway that plays a key role in cell homeostasis through its regulatory function in apoptosis, cell growth and cell cycle, and angiogenesis.